The role of lncRNA NEAT1 in human cancer chemoresistance.

Chemotherapy is currently one of the most effective methods in clinical cancer treatment. However, chemotherapy resistance is an important reason for poor chemotherapy efficacy and prognosis, which has become an urgent problem to be solved in the field of cancer chemotherapy. Therefore, it is very important to deeply study and analyze the mechanism of cancer chemotherapy resistance and its regulatory factors. Long non-coding RNA nuclear paraspeckle assembly transcript 1 (LncRNA NEAT1) has been shown to be closely associated with chemotherapy resistance in cancer. NEAT1 induces cancer cell resistance to chemotherapeutic drugs by regulating cell apoptosis, cell cycle, drug transport and metabolism, DNA damage repair, EMT, autophagy, cancer stem cell characteristics, and metabolic reprogramming. This indicates that NEAT1 may be an important target to overcome chemotherapy resistance and is expected to be a potential biomarker to predict the effect of chemotherapy. This article summarizes the expression characteristics and clinical characteristics of NEAT1 in different cancers, and deeply discusses the regulatory role of NEAT1 in cancer chemotherapy resistance and related molecular mechanisms, aiming to clarify NEAT1 as a new target to overcome cancer chemotherapy resistance and the feasibility of chemotherapy sensitizers, with a view to providing a potential therapeutic direction for overcoming the dilemma of cancer resistance in the future.

miR-145 inhibits aerobic glycolysis and cell proliferation of cervical cancer by acting on MYC.

Nearly half a million women are diagnosed with cervical cancer (CC) each year, with the incidence of CC stabilizing or rising in low-income and middle-income countries. Cancer cells use metabolic reprogramming to meet the needs of rapid proliferation, known as the Warburg effect, but the mechanism of the Warburg effect in CC remains unclear. microRNAs (miRNAs) have a wide range of effects on gene expression and diverse modes of action, and they regulate genes for metabolic reprogramming. Dysregulation of miRNA expression leads to metabolic abnormalities in tumor cells and promotes tumorigenesis and tumor progression. In this study, we found that miR-145 was negatively correlated with metabolic reprogramming-related genes and prevented the proliferation and metastasis of CC cell lines by impeding aerobic glycolysis. A dual-luciferase reporter assay showed that miR-145 can bind to the 3'-untranslated region (3'-UTR) of MYC. Chromatin Immunoprecipitation-quantitative real-time PCR indicated that MYC was involved in the regulation of glycolysis-related genes. In addition, miR-145 mimics significantly suppressed the growth of CC cell xenograft tumor, prolonged the survival time of mice, and dramatically silenced the expression of tumor proliferation marker Ki-67. Therefore, the results suggested that miR-145 affects aerobic glycolysis through MYC, which may be a potential target for the treatment of CC.

Association of inflammatory cytokines expression in cerebrospinal fluid with the severity and prognosis of spontaneous intracerebral hemorrhage.

OBJECTIVE: To investigate the potential diagnostic and prognostic implications of inflammatory cytokine levels in the cerebrospinal fluid (CSF) of patients with spontaneous intracerebral hemorrhage (SICH) upon their initial hospital admission. METHODS: Our cohort included 100 patients diagnosed with acute SICH, presenting to the Department of Neurosurgery. Additionally, we recruited 50 individuals without central nervous system (CNS) pathology, treated concurrently at our facility, as controls. CSF samples, collected upon hospital entry, were quantitatively assessed for 10 inflammatory cytokines using the Mesoscale Discovery Platform (MSD, Rockville, MD, USA) electrochemiluminescence technology, followed by validation through enzyme-linked immunosorbent assay (ELISA). RESULTS: We observed a marked elevation of IL-6, IL-8, IL-10, and TNF-α in the CSF of the SICH subgroup compared to controls. Higher Glasgow Coma Scale (GCS) scores in SICH patients corresponded with lower CSF concentrations of IL-6, IL-8, IL-10, and TNF-α, indicating an inverse relationship. Notably, CSF inflammatory cytokine levels were consistently higher in SICH patients with hydrocephalus than in those without. Increases in IL-6, IL-8, IL-10, and TNF-α in the CSF were notably more pronounced in the poor prognosis group (Glasgow Outcome Scale, GOS 1-3) compared to those with a favorable prognosis (GOS 4-5). The AUC values for these cytokines in predicting SICH prognosis were 0.750, 0.728, 0.717, and 0.743, respectively. CONCLUSIONS: Initial CSF levels of IL-6, IL-8, IL-10, and TNF-α upon admission provide significant insights into the severity of neural damage and are robust indicators for prognosis in SICH patients.

The role of lncRNA HCG18 in human diseases.

A substantial number of long noncoding RNAs (lncRNAs) have been identified as potent regulators of human disease. Human leukocyte antigen complex group 18 (HCG18) is a new type of lncRNA that has recently been proven to play an important role in the occurrence and development of various diseases. Studies have found that abnormal expression of HCG18 is closely related to the clinicopathological characteristics of many diseases. More importantly, HCG18 was also found to promote disease progression by affecting a series of cell biological processes. This article mainly discusses the expression characteristics, clinical characteristics, biological effects and related regulatory mechanisms of HCG18 in different human diseases, providing a scientific theoretical basis for its early clinical application.

In silico analyses and experimental validation of the MHC class-I restricted epitopes of Ebolavirus GP.

Ebolavirus (EBOV) causes an extremely high mortality and prevalence disease called Ebola virus disease (EVD). There is only one glycoprotein (GP) on the virus particle surface, which mediates entry into the host cell. Major histocompatibility complex (MHC) class-I restricted cluster of differentiation 8 (CD8+) T cell responses are important antiviral immune responses. Therefore, it is of great importance to understand EBOV GP-specific MHC class-I restricted epitopes within immunogenicity. In this study, computational approaches were employed to predict the dominant MHC class-I molecule epitopes of EBOV GP for mouse H2 and major alleles of human leukocyte antigen (HLA) class-I supertypes. Our results yielded 42 dominant epitopes in H2 haplotypes and 301 dominant epitopes in HLA class-I haplotypes. After validation by enzyme-linked immunospot (ELISpot) assay, in-depth analyses to ascertain their nature of conservation, immunogenicity, and docking with the corresponding MHC class-I molecules were undertaken. Our study predicted MHC class-I restricted epitopes that may aid the advancement of anti-EBOV immune responses. An integrated strategy of epitope prediction, validation and comparative analyses was postulated, which is promising for epitope-based immunotherapy development and application to viral epidemics.

MS2 device: smartphone-facilitated mobile nucleic acid analysis on microfluidic device.

Mobile sensing based on the integration of microfluidic devices and smartphones, so-called MS2 technology, has enabled many applications over recent years and continues to stimulate growing interest in both research communities and industries. In particular, MS2 technology has been proven to be able to be applied to molecular diagnostic analysis and can be implemented for basic research and clinical testing. However, the currently reported MS2-based nucleic acid analysis system has limited use in practical applications, because it is not integrated with quantitative PCR, multiplex PCR, and isothermal amplification functions, and lacks temperature control, image acquisition and real-time processing units with excellent performance. To provide a more universal and powerful platform, we here developed a novel MS2 device by integrating a thermocycler, a multi fluorescence detection unit, a PCR chip, an isothermal chip, and a smartphone. The MS2 device was approximately 325 mm (L) × 200 mm (W) × 200 mm (H) in volume and only 5 kg in weight, and showed an average power consumption of about 38.4 W. The entire nucleic acid amplification and analysis could be controlled through a self-made smartphone App. The maximum heating and cooling rates were 5 °C s-1 and 4 °C s-1, respectively. The entire PCR could be completed within 65 min. The temperature uniformity was less than 0.1 °C. Besides, the temperature stability over time (30 min) was within ±0.04 °C. Four optical channels were integrated (FAM, HEX, TAMRA, and ROX) on the MS2 device. In particular, the PCR-based detection sensitivity reached 1 copy per µL, and the amplification efficiency was calculated to be 106.8%. Besides, the MS2 device also was compatible with multiplex PCR and isothermal amplification. In short, the MS2 device showed performance consistent with that of traditional commercial equipment. Thus, the MS2 device provides an easy and integrated experimental platform for molecular diagnostic-related research and potential medical diagnostic applications.

Gamma-aminobutyric acid regulates glucose homeostasis and enhances the hepatopancreas health of juvenile Chinese mitten crab (Eriocheir sinensis) under fasting stress.

The ability of immune defense and resistance to physiological stress is crucial to animal health and survival. This study investigated the regulation of γ-aminobutyric acid (GABA) on metabolic homeostasis and its enhancement of hepatopancreas health in juvenile Chinese mitten crab (Eriocheir sinensis) under food deprivation. Juvenile crabs of 400 individuals were divided into four treatment groups: a control group without injection, and injections with a phosphate-buffered saline solution, 100 µmol GABA/mL and 1000 µmol GABA/mL, respectively. Hypoglycemia was induced by fasting, whereas the GABA treatment regulated hemolymph glucose homeostasis. The quantitative real-time PCR (qRT-PCR) results showed that the GABA treatment significantly up-regulated the mRNA expression levels of crustacean hyperglycemic hormone (CHH) and pyruvate kinase (PK). In contrast, the expression of E. sinensis insulin-like peptide (EsILP) was significantly down-regulated in the cranial ganglia, thoracic ganglia and hepatopancreas. Moreover, acid phosphatase (ACP), alkaline phosphatase (AKP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were significantly increased in the hepatopancreas by the GABA treatment. Furthermore, the hemocyanin content in serum was significantly increased with the GABA injection, and the glutathione (GSH) content, total superoxide dismutase (T-SOD) activity and catalase (CAT) activity in the hepatopancreas showed a similar increasing trend with the dose elevation of GABA. Therefore, these results indicate that GABA can effectively maintain the hemolymph glucose homeostasis by regulating the levels of glucose metabolism-related hormones and key enzymes to promote the degradation and utilization of hepatopancreas glycogen. Meanwhile, GABA can improve the hepatopancreas function and immune status of juvenile E. sinensis under fasting stress. The treatment with GABA may provide a clue to guide health management in crab farming.

High-accuracy and high-repeatability measurement of the cut error of a nonlinear uniaxial crystal.

To accurately determine the optical axis cut error of a nonlinear uniaxial crystal, a measurement method based on dual-optical path second-harmonic energy (SHE) rocking curve acquisition is presented in, of which the measurement uncertainty can be controlled within 3.20 µrad , 26 times higher than that of a high-precision commercial x-ray diffractometer (XRD). To meet the measurement requirements, a Type I potassium dihydrogen phosphate reference crystal (RC) is first made, and its optical axis cut error is considered as a reference. Then, the optical axis cut error of a measured crystal (MC) with an aperture of 25mm×25mm and a thickness of 10 mm is determined by simultaneously recording the SHE scatter plots of the RC and the MC, where the measurement repeatability of 10 consecutive measurements is only 4.48 µrad and the measurement speed is within 20 s. During data processing, a third-order Fourier polynomial is proposed to fit the scatter plots into smooth curves, of which the regression coefficients are greater than 0.9975. The experimental method not only overcomes the shortcomings that XRDs will introduce scratches and defects to the crystal surface and are unable to measure large-aperture crystals, but can be used to guide the production of precise cutting of a nonlinear uniaxial crystal, thus ensuring the maximum conversion efficiency of a frequency multiplication system.

Preventing forgery attacks in computational ghost imaging or disabling ghost imaging in a "spatiotemporal" scattering medium with weighted multiplicative signals.

The ghost imaging (GI) approach is an intriguing and promising image acquisition technique that can transmit high-quality image information in a scattering environment. In this paper, we focus on two concerns recently emerged in the GI modality: one is the vulnerability to forgery attacks in GI-based optical encryption [Opt. Lett.45, 3917 (2020)OPLEDP0146-959210.1364/OL.392424], and the other is the potential threat of GI to personal privacy regarding non-invasive imaging [Opt. Express28, 17232 (2020)OPEXFF1094-408710.1364/OE.391788]. The core idea is to recommend introducing weighted multiplicative signals [Opt. Express27, 36505 (2019)OPEXFF1094-408710.1364/OE.27.036505] into the computational GI system, whether on the transmitting end or the receiving end. At the transmitting end, the random multiplicative signal can be used as an additional key that can reduce the possibility of forgery attacks, thereby increasing image transmission security. On the receiving end, the introduction of a random multiplicative signal to a spatial scattering medium makes it a "spatiotemporal" scattering medium, whose transmittance changes with time. Further, the spatiotemporal scattering medium can disable direct imaging and GI at the same time with low cost, thereby having great potential in privacy protection in daily lives.

Relationship Between Undergraduate Nursing Students' Self-directed Learning and Training Demands for Nursing Information Systems: A Cross-sectional Study.

Self-directed learning refers to an approach to acquiring knowledge and skills in which learners take responsibility for themselves. Currently, it is a feasible way to familiarize with nursing information systems, which are essential components of hospital information systems and widely used in clinical nursing. This study assessed undergraduate nursing students' self-directed learning of nursing information systems and explored influencing factors, using a cross-sectional design and a convenience sample. Participants voluntarily completed a general information questionnaire, a training demands questionnaire for nursing information systems, and the Self-rating Scale for Self-directed Learning, which measured the level of self-directed learning. A total of 353 valid surveys were analyzed, among which 51.8% agreed with the necessity of mastering nursing information systems. Nursing students present a moderate level of self-directed learning, with an advantage in interpersonal skills and a deficiency in learning activities. Students' training demands, confidence in using nursing information systems in clinical practice, attitude toward nursing as a career, and academic performance were identified as predictors of self-directed learning for nursing information systems. Future cross-national research, studies about other factors, and ways to improve formal education are needed.

Mesoporous anion-cation-codoped Co9S8 nanorings for enhanced electrocatalytic oxygen evolution reactions.

Recently, the design and synthesis of Co9S8 micro/nanostructures have attracted attention as electrochemical energy storage and conversion devices due to their low cost and environmental friendliness. Herein, Co9S8 nanorings were synthesized via a one-step solvothermal method with the incorporation of Fe ions, subsequently, properly selenized to boost their electrocatalytic performance. The morphology and structure of the series of cation and anion regulated Co9S8 nanorings were characterized, the electrochemical oxygen evolution reaction (OER) properties were assessed. It is worth noting that the as-prepared catalysts, especially the innovative Fe and Se ions double doped Co9S8 nanorings, denoted as Se/Fe-Co9S8-0.14, exhibited good electrocatalytic OER performance with low overpotential (298 mV) and high durability under alkaline conditions. This work provides a new perspective to develop non-noble metal Co9S8-based OER electrocatalysts with a superior electrocatalytic performance.

Effects of Perineal Warm Compresses during the Second Stage of Labor on Reducing Perineal Trauma and Relieving Postpartum Perineal Pain in Primiparous Women: A Systematic Review and Meta-Analyses.

Non-pharmaceutical midwifery techniques, including perineal warm compresses, to improve maternal outcomes remain controversial. The aims of this study are to assess the effects of perineal warm compresses on reducing perineal trauma and postpartum perineal pain relief. This systematic review included randomized controlled trials (RCTs). We searched seven bibliographic databases, three RCT register websites, and two dissertation databases for publications from inception to 15 March 2023. Chinese and English publications were included. Two independent reviewers conducted the risk of bias assessment, data extraction, and the evaluation of the certainty of the evidence utilizing the Cochrane risk of bias 2.0 assessment criteria, the Review Manager 5.4, and the online GRADEpro tool, respectively. Seven RCTs involving 1362 primiparous women were included. The combined results demonstrated a statistically significant reduction in the second-, third- and/or fourth- degree perineal lacerations, the incidence of episiotomy, and the relief of the short-term perineal pain postpartum (within two days). There was a potential favorable effect on improving the integrity of the perineum. However, the results did not show a statistically significant supportive effect on reducing first-degree perineal lacerations and the rate of perineal lacerations requiring sutures. In summary, perineal warm compresses effectively reduced the second-, third-/or fourth-degree perineal trauma and decreased the short-term perineal pain after birth.

Topological regularization of networks in temporal lobe epilepsy: a structural MRI study.

Objective: Patients with temporal lobe epilepsy (TLE) often exhibit neurocognitive disorders; however, we still know very little about the pathogenesis of cognitive impairment in patients with TLE. Therefore, our aim is to detect changes in the structural connectivity networks (SCN) of patients with TLE. Methods: Thirty-five patients with TLE were compared with 47 normal controls (NC) matched according to age, gender, handedness, and education level. All subjects underwent thin-slice T1WI scanning of the brain using a 3.0 T MRI. Then, a large-scale structural covariance network was constructed based on the gray matter volume extracted from the structural MRI. Graph theory was then used to determine the topological changes in the structural covariance network of TLE patients. Results: Although small-world networks were retained, the structural covariance network of TLE patients exhibited topological irregularities in regular architecture as evidenced by an increase in the small world properties (p < 0.001), normalized clustering coefficient (p < 0.001), and a decrease in the transfer coefficient (p < 0.001) compared with the NC group. Locally, TLE patients showed a decrease in nodal betweenness and degree in the left lingual gyrus, right middle occipital gyrus and right thalamus compared with the NC group (p < 0.05, uncorrected). The degree of structural networks in both TLE (Temporal Lobe Epilepsy) and control groups was distributed exponentially in truncated power law. In addition, the stability of random faults in the structural covariance network of TLE patients was stronger (p = 0.01), but its fault tolerance was lower (p = 0.03). Conclusion: The objective of this study is to investigate the potential neurobiological mechanisms associated with temporal lobe epilepsy through graph theoretical analysis, and to examine the topological characteristics and robustness of gray matter structural networks at the network level.

Quantitative proteomic and metabolomic profiling reveals different osmoregulation mechanisms of tilapia cells coping with different hyperosmotic stress.

This study aimed to investigate the different regulatory mechanisms of euryhaline fish under regular hyperosmotic and extreme hyperosmotic stress. The OmB (Oreochromis mossambicus brain) cells were exposed to three treatments: control, regular hyperosmotic stress and extreme hyperosmotic stress. After 12 h exposure, proteomics, metabolomics analyses and integrative analyses were explored. Both kinds of stress lead to lowering cell growth and morphology changes, while under regular hyperosmotic stress, the up-regulated processes related with compatible organic osmolytes synthesis are crucial strategy for the euryhaline fish cell line to survive; On the other hand, under extreme hyperosmotic stress, the processes related with cell apoptosis and cell cycle arrest are dominant. Furthermore, down-regulated pyrimidine metabolism and several ribosomal proteins partially participated in the lowered cell metabolism and increased cell death under both kinds of hyperosmotic stress. The PI3K-Akt and p53 signaling pathways were involved in the stagnant stage of cell cycles and induction of cell apoptosis under both kinds of hyperosmotic stress. However, HIF-1, FoxO, JAK-STAT and Hippo signaling pathways mainly contribute to disrupting the cell cycle, metabolism and induction of cell apoptosis under extreme hyperosmotic stress. SIGNIFICANCE: In the past, the research on fish osmoregulation mainly focused on the transcription factors and ion transporters of osmoregulation, the processes between osmotic sensing and signal transduction, and the associations between signaling pathways and regulation processes have been poorly understood. Investigating fish cell osmoregulation and potential signal transduction pathways is necessary. With the advancements in omics research, it is now feasible to investigate the relationship between environmental stress and molecular responses. In this study, we aimed to explore the signaling pathways and substance metabolism mode during hyper-osmoregulation in OmB cell line, to reveal the key factors that are critical to cell osmoregulation.

Impact of the Built Environment on Residents' Health: Evidence from the China Labor Dynamics Survey in 2016.

In the process of China's rapid urbanization, the health level of residents has been improved to a great extent. However, with the expansion of urban scale and spatial restructuring, a series of urban environmental problems have posed new challenges to public health. However, the impact of the built environment on residents' health is controversial, and the applicability of the conclusions based on western urban sprawl in China is not clear enough. In addition, the exploration of the impact path of the built environment on health is still not comprehensive and in-depth. Based on the China Labor Dynamics Survey (CLDS) in 2016 and relevant statistical yearbook data, this study explored the impact of the built environment at community and urban scale on residents' health and its age heterogeneity and further explored the mediating role of physical exercise, neighborhood support, and community safety. According to the research, the urban and community-built environment has significant impacts on residents' health, and the impact is significantly different at different scales. In addition, there is a significant difference in the impact of built environment factors on residents' health among populations with different life cycles. From the perspective of the impact path, greening coverage can improve residents' self-rated health by enhancing the perceived safety of living in the community. In contrast, the high community population density will not only weaken the degree of neighborhood support but also reduce the perception level of community residential safety, thus damaging residents' health. In short, from the perspective of environmental intervention, the previously mentioned results put forward possible suggestions on strengthening the construction of a healthy living environment so as to maximize the health effectiveness of cities and communities.

Flexible nanofibrous membranes of dual metallic metal-organic framework with enhanced Lewis basic sites and high loading mass for efficient CO2 capture.

Excessive CO2 emissions and the resultant global warming present significant environmental challenges, posing threats to human health and public safety. Metal-organic frameworks (MOFs), known for their high specific area and large porosity, hold the promise for CO2 capture. However, a major obstacle is the low loading mass of MOFs and the limited interface affinity and compatibility between MOFs and substrates. In this study, we present an electrospinning-assisted in-situ synthesis dual metallic framework strategy for preparing flexible Zn/Co-ZIF nanofibrous membranes (NFMs). This method achieves the high loading mass of MOFs and introduces abundant Lewis basic sites, thereby enhancing the CO2 adsorption. The dual metallic Zn/Co-ZIF NFMs exhibit remarkable features, including high MOF loading mass (70.23 wt%), high specific surface area (379.63 m2g-1), large porosity (92.34 %), high CO2 adsorption capacity (4.43 mmol/g), high CO2/N2 adsorption selectivity (37), and high CO2/CH4 adsorption selectivity (31). Moreover, the dual metallic Zn/Co-ZIF NFMs demonstrate robust structural stability and durability attributed to the excellent interface affinity between MOFs and NFMs, retaining 96.56 % of their initial capacity after 10 adsorption-desorption cycles. This work presents a prospective direction for developing flexible dual metallic MOF NFMs for the efficient capture of CO2.

Mkit: A mobile nucleic acid assay based on a chitosan-modified minimalistic microfluidic chip (CM3-chip) and smartphone.

Mobile sensing enabled by MS2 technology, which integrates microfluidic and smartphone components, has seen many applications in recent years. In this direction, we developed an MS2 platform (an integrated kit) for nucleic acid assay, which included a chitosan-modified minimalistic microfluidic chip (CM3-chip), a smartphone-based fluorescence detector (SF-detector), an APP for imaging and analysis, reagents, and accessories. Once the lysed sample was loaded into the CM3-chip modified by 1% concentration and 200-260 kDa molecular weight of chitosan, the following assay can be completed in approximately 1 h. The Mkit can detect 3 × 10° copies µL-1 of plasmid DNA and its polymerase chain reaction (PCR) efficiency was 96.8%. The CM3-chip equipped for the Mkit can enrich nucleic acid from the pH = 5 of lysis buffer, instead of using conventional adsorption mediums such as the magnetic beads and silica gel membranes, which could result in unexpected impurity residuals and tedious cleaning operations. In addition, the performance of the Mkit equipped with the pristine chip was demonstrated to perform poorer than that coupled with the CM3-chip in which the enriched nucleic acid can be all used for "in-situ PCR". The universality, selectivity, and user-friendliness of the Mkit were also validated. We finally demonstrated the feasibility of the Mkit for testing artificially prepared infected samples. H5N6 and IAV-infected saliva samples provided the limits of detection of 5 × 102 copies mL-1 and 3.24 × 102 copies mL-1 per chamber, respectively. The streamlined assay and compact device should enable the great potential of the Mkit in research and potential diagnostic uses.

[Regulation of intracellular level of ATP and NADH in Escherichia coli to promote succinic acid production].

Succinic acid is an important C4 platform chemical that is widely used in food, chemical, medicine sectors. The bottleneck of fermentative production of succinic acid by engineered Escherichia coli is the imbalance of intracellular cofactors, which often leads to accumulation of by-products, lower yield and low productivity. Stoichiometric analysis indicated that an efficient production of succinic acid by E. coli FMME-N-26 under micro-aeration conditions might be achieved when the TCA cycle provides enough ATP and NADH for the r-TCA pathway. In order to promote succinic acid production, a serial of metabolic engineering strategies include reducing ATP consumption, strengthening ATP synthesis, blocking NADH competitive pathway and constructing NADH complementary pathway were developed. As result, an engineered E. coli FW-17 capable of producing 139.52 g/L succinic acid and 1.40 g/L acetic acid in 5 L fermenter, which were 17.81% higher and 67.59% lower than that of the control strain, was developed. Further scale-up experiments were carried out in a 1 000 L fermenter, and the titer of succinic acid and acetic acid were 140.2 g/L and 1.38 g/L, respectively.

Engineering growth phenotypes of Aspergillus oryzae for L-malate production.

Improving the growth status of Aspergillus oryzae is an efficient way to enhance L-malate production. However, the growth mechanism of filamentous fungi is relatively complex, which limits A. oryzae as a cell factory to produce L-malate industrially. This study determined the relationship between growth status and L-malate production. The optimal ranges of colony diameter, percentage of vegetative mycelia, and pellet number of A. oryzae were determined to be 26-30 mm, 35-40%, and 220-240/mL, respectively. To achieve this optimum range, adaptive evolution was used to obtain the evolved strain Z07 with 132.54 g/L L-malate and a productivity of 1.1 g/L/h. Finally, a combination of transcriptome analysis and morphological characterization was used to identify the relevant pathway genes that affect the growth mechanism of A. oryzae. The strategies used in this study and the growth mechanism provide a good basis for efficient L-malate production by filamentous fungi.

IGF2BP2 promotes colorectal cancer progression by upregulating the expression of TFRC and enhancing iron metabolism.

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive system, ranking third for morbidity and mortality worldwide. At present, no effective control method is available for this cancer type. In tumor cells, especially iron metabolization, is necessary for its growth and proliferation. High levels of iron are an important feature to maintain tumor growth; however, the overall mechanism remains unclear. METHODS: We used western blotting, immunohistochemistry (IHC) and real-time quantitative PCR to analyze the expression of IGF2BP2 in cell lines and tissues. Further, RNA-sequencing, RNA immunoprecipitation and methylated RNA immunoprecipitation experiments explored the specific binding of target genes. Moreover, the RNA stability assay was performed to determine the half-life of genes downstream of IGF2BP2. In addition, the Cell Counting Kit-8, colony formation assay, 5-ethynyl-2'-deoxyuridine assay and flow cytometry were used to evaluate the effects of IGF2BP2 on proliferation and iron metabolism. Lastly, the role of IGF2BP2 in promoting CRC growth was demonstrated in animal models. RESULTS: We observed that IGF2BP2 is associated with iron homeostasis and that TFRC is a downstream target of IGF2BP2. Further, overexpression of TFRC can rescue the growth of IGF2BP2-knockdown CRC cells. Mechanistically, we determined that IGF2BP2 regulates TFRC methylation via METTL4, thereby regulating iron metabolism and promoting CRC growth. Furthermore, using animal models, we observed that IGF2BP2 promotes CRC growth. CONCLUSION: IGF2BP2 regulates TFRC mRNA methylation via METTL4, thereby regulating iron metabolism and promoting CRC growth. Our study highlights the key roles of IGF2BP2 in CRC carcinogenesis and the iron transport pathways.